Tumor-related leucocytosis and chemotherapy-induced neutropenia: linked or independent prognostic factors for advanced non-small cell lung cancer?

Tumor-related leucocytosis is a paraneoplastic syndrome that is encountered occasionally in the clinical course of patients with non-small cell lung cancer (NSCLC). Autonomous production of hematopoietic cytokines (granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor) has been identified in some of the patients presenting with this syndrome. In addition to the widely accepted prognostic factors of performance status and disease stage, recently, leucocytosis has been found to be a significant negative prognostic factor for overall survival and time to progression in patients with advanced-stage NSCLC in a pooled analysis of North Central Cancer Treatment Group trials, with data from about 1000 patients. A pooled analysis of an Italian Group with data from about 1300 patients has recently shown that neutropenia during chemotherapy is associated with increased survival of patients with advanced NSCLC. Similar results on the independent prognostic value of chemotherapy-induced neutropenia, have been reported by the Hellenic Oncology Research Group in a retrospective analysis on 850 patients. The absence of chemotherapy-induced neutropenia can be interpreted as a result of chemotherapy-underdosing. However, considering the negative prognostic value of leucocytosis, another interpretation should be ruled out: a proportion of the patients who do not experience chemotherapy-induced neutropenia may be associated with a worst prognosis because they may be characterized by base-line tumor-related leucocytosis and autonomous production of hematopoietic cytokines protecting them from chemotherapy-induced neutropenia. Prospective trials are needed to assess if NSCLC-related leucocytosis and chemotherapy-induced neutropenia are two linked or independent prognostic factors for NSCLC. This paper is a review of the available retrospective evidence on the aetiology and prognostic value of tumor-related leucocytosis and on the prognostic value of chemotherapy-induced neutropenia in advanced NSCLC. Moreover we try to hypothesize a possible correlation between these two phenomena and to give suggestions on the prospective evaluation of this hypothetical correlation in the next future.